Detection of Brain Tumor Cells in the Peripheral Blood by a Telomerase Promoter-Based Assay

MacArthur, Kelly M.; Kao, Gary D.; Chandrasekaran, S.; Alonso‐Basanta, Michelle; Chapman, Christina H.; Lustig, Robert A.; Wileyto, E. Paul; Hahn, Stephen M.; Dorsey, Jay F.

doi:10.1158/0008-5472.can-13-0813

Cited by 155 publications

(173 citation statements)

References 25 publications

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“…[27] Recent studies reported that the number of circulating tumor cells in the blood of glioma patients is approximately 10 cells ml –1 . [28,29]. These suggest that there is a possibility that the IDH1 status can be determined with our device using cerebrospinal fluid and blood.…”

Section: Discussionmentioning

confidence: 94%

An immuno-wall microdevice exhibits rapid and sensitive detection of IDH1-R132H mutation specific to grade II and III gliomas

Yamamichi

Kasama

Ohka

et al. 2016

Science and Technology of Advanced Materials

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World Health Organization grade II and III gliomas most frequently occur in the central nervous system (CNS) in adults. Gliomas are not circumscribed; tumor edges are irregular and consist of tumor cells, normal brain tissue, and hyperplastic reactive glial cells. Therefore, the tumors are not fully resectable, resulting in recurrence, malignant progression, and eventual death. Approximately 69–80% of grade II and III gliomas harbor mutations in the isocitrate dehydrogenase 1 gene (IDH1), of which 83–90% are found to be the IDH1-R132H mutation. Detection of the IDH1-R132H mutation should help in the differential diagnosis of grade II and III gliomas from other types of CNS tumors and help determine the boundary between the tumor and normal brain tissue. In this study, we established a highly sensitive antibody-based device, referred to as the immuno-wall, to detect the IDH1-R132H mutation in gliomas. The immuno-wall causes an immunoreaction in microchannels fabricated using a photo-polymerizing polymer. This microdevice enables the analysis of the IDH1 status with a small sample within 15 min with substantially high sensitivity. Our results suggested that 10% content of the IDH1-R132H mutation in a sample of 0.33 μl volume, with 500 ng protein, or from 500 cells is theoretically sufficient for the analysis. The immuno-wall device will enable the rapid and highly sensitive detection of the IDH1-R132H mutation in routine clinical practice.

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Section: Discussionmentioning

confidence: 94%

An immuno-wall microdevice exhibits rapid and sensitive detection of IDH1-R132H mutation specific to grade II and III gliomas

Yamamichi

Kasama

Ohka

et al. 2016

Science and Technology of Advanced Materials

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“…Thus, the identification of glioma-derived CTCs in the circulation of such patients posttreatment (after chemoradiation therapy) is prognostic, with a reduction in CTCs indicating treatment response and an increase in CTCs indicating disease progression (44,45). …”

Section: Discussionmentioning

confidence: 99%

A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas

et al. 2016

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The aims of the present study were to undertake gene expression profiling of the blood of glioma patients to determine key genetic components of signaling pathways and to develop a panel of genes that could be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples. In this study, blood samples were obtained from glioma patients, non-glioma and control subjects. Ten samples each were obtained from patients with high and low grade tumours, respectively, ten samples from non-glioma patients and twenty samples from control subjects. Total RNA was isolated from each sample after which first and second strand synthesis was performed. The resulting cRNA was then hybridized with the Agilent Whole Human Genome (4×44K) microarray chip according to the manufacturer's instructions. Universal Human Reference RNA and samples were labeled with Cy3 CTP and Cy5 CTP, respectively. Microarray data were analyzed by the Agilent Gene Spring 12.1V software using stringent criteria which included at least a 2-fold difference in gene expression between samples. Statistical analysis was performed using the unpaired Student's t-test with a P<0.01. Pathway enrichment was also performed, with key genes selected for validation using droplet digital polymerase chain reaction (ddPCR). The gene expression profiling indicated that were a substantial number of genes that were differentially expressed with more than a 2-fold change (P<0.01) between each of the four different conditions. We selected key genes within significant pathways that were analyzed through pathway enrichment. These key genes included regulators of cell proliferation, transcription factors, cytokines and tumour suppressor genes. In the present study, we showed that key genes involved in significant and well established pathways, could possibly be used as a potential blood-based biomarker to differentiate between high and low grade gliomas, non-gliomas and control samples.

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“…This might lead to suboptimal induction of immune response to tumors located in the brain as compared to other sites. Nonetheless, it cannot be entirely excluded that immune responses to brain tumors are elicited in the periphery in response to circulating tumor cells reaching secondary lymphoid organs; these having been reported in a significant number of patients with GBM (82, 83). …”

Section: Immune Responses To Tumors Arising In the Brainmentioning

confidence: 99%

Immunotherapy of Malignant Tumors in the Brain: How Different from Other Sites?

et al. 2016

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Immunotherapy is now advancing at remarkable pace for tumors located in various tissues, including the brain. Strategies launched decades ago, such as tumor antigen-specific therapeutic vaccines and adoptive transfer of tumor-infiltrating lymphocytes are being complemented by molecular engineering approaches allowing the development of tumor-specific TCR transgenic and chimeric antigen receptor T cells. In addition, the spectacular results obtained in the last years with immune checkpoint inhibitors are transfiguring immunotherapy, these agents being used both as single molecules, but also in combination with other immunotherapeutic modalities. Implementation of these various strategies is ongoing for more and more malignancies, including tumors located in the brain, raising the question of the immunological particularities of this site. This may necessitate cautious selection of tumor antigens, minimizing the immunosuppressive environment and promoting efficient T cell trafficking to the tumor. Once these aspects are taken into account, we might efficiently design immunotherapy for patients suffering from tumors located in the brain, with beneficial clinical outcome.

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Detection of Brain Tumor Cells in the Peripheral Blood by a Telomerase Promoter-Based Assay

Cited by 155 publications

References 25 publications

An immuno-wall microdevice exhibits rapid and sensitive detection of IDH1-R132H mutation specific to grade II and III gliomas

An immuno-wall microdevice exhibits rapid and sensitive detection of IDH1-R132H mutation specific to grade II and III gliomas

A blood-based gene expression and signaling pathway analysis to differentiate between high and low grade gliomas

Immunotherapy of Malignant Tumors in the Brain: How Different from Other Sites?

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